Adverse Drug Reactions

Question 1

What is an adverse drug reaction?

Answer 1

Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or treatment

Question 2

Common drugs involved:

Answer 2

• Antibiotics
• Antineoplastics
• Anticoagulants
• Cardiovascular drugs
• Hypoglycaemics
• Antihypertensives
• NSAID/Analgesics
• Diagnostic agents
• CNS drugs (neuro and psych)

Question 3

Body systems commonly involved:

Answer 3

• Haematologic
• CNS
• Dermatologic/allergic
• Metabolic
• Cardiovascular
• Gastrointestinal
• Renal/genitourinary
• Respiratory
• Sensory

Question 4

ADR risk factors

Answer 4

• Age
• Multiple medications
• Multiple co-morbid conditions
• Inappropritate medication prescribing use or monitoring
• End-organ dysfunction
• Altered physiology
• Prior history of ADRs
• Extent (dose) and duration of exposure
• Genetic predisposition

Question 5

Frequency of ADRs

Answer 5

• 10-20% of all inpatients suffer an adverse drug reaction
• 6.5% of hospital admissions occur as a result of an ADR
• 4th leading cause of death

Question 6

Classification of onset of ADRs

Answer 6

• Acute: within 60 minutes, bronchoconstriction
• Sub-acute: 1 to 24 hours. Rash, serum sickness
• Latent: >2 days. Eczematous eruptions

Question 7

Classification of severity of ADRs

Answer 7

• Mild: bothersome but requires no change in therapy
• Moderate: requires change in therapy, additional treatment, hospitalisation
• Severe: Disabling or life-threatening, kidney failure

Question 8

Type A ADR

Answer 8

• Augmented
• Dose related
• Predictable can often be unrelated to primary effect
• Resolve when the drug is reduced or stopped
• Recognised before a drug is available

Question 9

Type B ADR

Answer 9

• Bizarre
• Idiosyncratic
• Unpredictable
• Rare
• Cause serious illness or death
• Unidentified for months or years
• Unrelated to dose

Question 10

Type C

Answer 10

• Chronic/long term effects
• Related to duration of treatment as well as dose.
• Semi-predictable
• Doesn’t occur with one dose

Question 11

Type D

Answer 11

• Delayed

- Adverse effects occur after some time e.g. children of treated patients or treated patients years after treatment

Question 12

Type E

Answer 12

• End of treatment effects

- Adverse effects when drug is stopped suddenly

Question 13

Type F

Answer 13

• Failure of treatment
• Common
• Dose related
• Frequently cause by drug interactions
• Failure of Oral Contraceptives when administered with hepatic enzyme inducers/antibiotics

Question 14

Examples of Type A ADR

Answer 14

• Galactorrhoea with domperidone

- Dry mouth with tricyclic antidepressants

Question 15

Reasons for Type A ADRs

Answer 15

• Too high a dose
• Pharmaceutical variation
  2 main ones:
• Pharmacokinetic (ADME)
• Pharmacodynamic variation
• Pharmacogenetic. 10% population slow metabolisers, can be prone to drug toxicity
• Disease: renal, hepatic, cardiac failure (oedomas in gut, decreased GFR, hepatic congestion)

Question 16

Factors that affect Type B reactions

Answer 16

• More common with macromolecules: protein, vaccine, polypeptides
• Patients with a history of asthma, eczema
• Presence of certain HLAs

Question 17

Immunological mechanisms of Type B

Answer 17

• No relation to the pharmacological action of the drug
• Delay between exposure and ADR
• No response curve
• Manifests as rash, asthma, serum sickness
• Idiosyncratic: inherent abnormal response, abnormal receptor activity

Question 18

Pharmacogenetic mechanisms of Type B

Answer 18

• Genetic
• Examples of genetic: enzyme abnormality. Erthythrocyte glucose-6-phosphate deydrogenase (G6PD) deficiency
• Susceptible to red cell haemolysis when given drugs such as primaquine and sulphonamides
• Receptor abnormality malignant hyperthermia with general anaesthetics

Also get immunological

Question 19

Examples of Type C reactions

Answer 19

• Iatrogen Cushings disease
• Steroid induced osteoporosis
• Opiate dependence
• Analgesic neuropathy due to paracemtaol or NSAIDS

Question 20

Examples of Type D reactions

Answer 20

• Teratogenesis: Craniofacial malformation in children with mothers who have been treated with isotretinoin
• Carcinogenesis: those treated with alkylating agents or immunosuppressive agents such as cyclophosphamide

Question 21

Examples of Type E reactions

Answer 21

• Unstable angina and MI when beta blockers are stopped
• Addisonian crisis when long term steroids suddenly stopped e.g. hypopituitism if you come off steroids and your adrenals are suppressed
• Withdrawal seizures when antiepileptics are stopped

Question 22

Rebound phenomena

Answer 22

• Alcohol
• Benzodiazepines
• Beta blockers
• Corticosteroids

Question 23

Diagnosis steps of ADR:

Answer 23

1. Differential diagnosis
2. Medication history (past and present)
3. Assess time of onset and dose relationship
4. Laboratory investigation: plasma concentration measurement and allergy tests

Question 24

How to report ADRs

Answer 24

- Yellow Cards
Collect info on:
- Side effects
- Medical device adverse incidents
- Defective medicines
- Counterfeit or fake medicines or medical devices